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Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.
- D. de Zeeuw, T. Akizawa, +17 authors G. Chertow
- The New England journal of medicine
- 25 December 2013
Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of end-stage renal disease (ESRD) or death from cardiovascular causes and was terminated on the recommendation of the independent data and safety monitoring committee. Expand
Bardoxolone methyl and kidney function in CKD with type 2 diabetes.
Bardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks, and the improvement persisted at 52 weeks, suggesting that bardoxlone methyl may have promise for the treatment of CKD. Expand
Anti-inflammatory Triterpenoid Blocks Immune Suppressive Function of MDSCs and Improves Immune Response in Cancer
- S. Nagaraj, Je-in Youn, +12 authors D. Gabrilovich
- Biology, Medicine
- Clinical Cancer Research
- 9 March 2010
CDDO-Me abrogated the immune suppressive effect of MDSCs and improved immune responses in tumor-bearing mice and cancer patients and may represent an attractive therapeutic option by enhancing the effect of cancer immunotherapy. Expand
Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1)-->signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3.
Findings indicate that CDDO-Me inhibits activation of the JAK1-->STAT3 pathway by forming adducts with both JAK2 and STAT3, and binds directly to STAT3 by a mechanism dependent on the alkylation of Cys(259). Expand
Diabetic Downregulation of Nrf2 Activity via ERK Contributes to Oxidative Stress–Induced Insulin Resistance in Cardiac Cells In Vitro and In Vivo
ERK-mediated suppression of Nrf2 activity leads to the oxidative stress–induced insulin resistance in adult cardiomyocytes and downregulated glucose utilization in the diabetic heart. Expand
Effect of Bardoxolone Methyl on Kidney Function in Patients with T2D and Stage 3b–4 CKD
- P. Pérgola, Melissa Krauth, +4 authors D. Warnock
- American Journal of Nephrology
- 21 April 2011
An apparent increase in kidney function is described following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function. Expand
A Phase I First-in-Human Trial of Bardoxolone Methyl in Patients with Advanced Solid Tumors and Lymphomas
Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer and suggesting that bardoxolone methyl might be beneficial in chronic kidney disease. Expand
Mechanisms Contributing to Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated with Bardoxolone Methyl
The totality of the evidence suggests that through modulation of the endothelin pathway, bardoxolone methyl may pharmacologically promote acute sodium and volume retention and increase blood pressure in patients with more advanced CKD. Expand
Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179.
The present studies show that CDDO and CDDO-Me block tumor necrosis factoralpha-induced targeting of NF-kappaB p65 to the nucleus and inhibits IkappaBalpha kinasebeta activity in cells. Expand
Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPARγ, and HO-1.
- Q. Q. Wu, Yanxia Wang, +11 authors Christopher Y. Lu
- American journal of physiology. Renal physiology
- 1 May 2011
It is reported that bardoxolone methyl (BARD) ameliorates ischemic murine AKI as assessed by both renal function and pathology, and it is suggested that BARD's effects on tubular and leukocyte HO-1 during isChemic AKI may be Nrf2 independent. Expand